A Comparative Study Of PF-06439535 Plus Paclitaxel-Carbop... | NCT02364999

ID	Type	Description	Link
2014-003878-16	EudraCT Number
B7391003	Other Identifier	Alias Study Number

Label	Type	Description	Intervention Names
Bevacizumab-Pfizer	Experimental	Bevacizumab-Pfizer plus paclitaxel and carboplatin	Drug: Bevacizumab-Pfizer Drug: Paclitaxel Drug: Carboplatin
Bevacizumab-EU	Active Comparator	Bevacizumab-EU plus paclitaxel and carboplatin	Drug: Bevacizumab-EU Drug: Paclitaxel Drug: Carboplatin

Name	Type	Description	Arm Group Labels	Other Names
Bevacizumab-Pfizer	Drug	Bevacizumab-Pfizer: 15 mg/kg IV on Day 1 of a 21-day cycle for each of at least 4 and no more than six (6) 21-day cycles, followed by the assigned blinded bevacizumab monotherapy.

Measure	Description	Time Frame
Objective Response Rate (ORR) by Week 19	ORR refers to percentage of participants who achieved complete response (CR) or partial response (PR) by Week 19 of the study in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 which was subsequently confirmed by Week 25. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved PR if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits.	25 weeks

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events	AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Southern Cancer Center, PC		Daphne	Alabama	36526	United States
Southern Cancer Center, PC

PubMed Identifier	Type	Citation	Retractions
31768697	Derived	Li CSW, Sweeney K, Cronenberger C. Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin(R)) in patients with advanced non-squamous non-small cell lung cancer. Cancer Chemother Pharmacol. 2020 Mar;85(3):487-499. doi: 10.1007/s00280-019-03946-8. Epub 2019 Nov 26.
31338773

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Mar 28, 2017	May 7, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Objective Response Rate (ORR) by Week 19

ORR refers to percentage of participants who achieved complete response (CR) or partial response (PR) by Week 19 of the study in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 which was subsequently confirmed by Week 25. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved PR if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits.

The Intent-to-Treat (ITT) population was used for analysis of ORR, and it included all participants who were randomized to study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

25 weeks

ID	Title	Description
OG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
OG001	Bevacizumab-EU	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.

Units	Counts
Participants	OG000358 OG001361

Title

Denominators

Categories

Title	Measurements
	OG00045.3(40.01 to 50.57) OG00144.6(39.40 to 49.89)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Risk Difference (RD)	0.6531			2-Sided	95	-6.6080	7.9082			PF-06439535 vs Bevacizumab-EU		Equivalence	Calculated based on 2-sided Miettinen and Nurminen method without strata for risk difference for confirmed response. EU equivalence margins (95% CI in -13% to 13%).
OG000 OG001

Secondary

Number of Participants With Treatment-Emergent Adverse Events

AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

The analysis population included all participants who were randomized and received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

55 weeks

ID	Title	Description
OG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.

Secondary

Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

Laboratory evaluation included hematology (hemoglobin, white blood cells, platelets and absolute neutrophil count), blood chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, serum or plasma creatinine, sodium, potassium, total calcium, magnesium, blood urea nitrogen or urea, and albumin ), coagulation (international normalized ratio for prothrombin time and activated partial thromboplastin time) and urinalysis (dipstick followed by a quantitative urine protein analysis for results of 2+ or greater).

The analysis population included all participants who were randomized and received at least 1 dose of study treatment, and had laboratory evaluation done.

Posted

Count of Participants

Participants

55 weeks

ID	Title	Description
OG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
OG001

Secondary

Duration of Response (DOR)

DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD. DOR was based on the Brookmeyer and Crowley method.

The analysis population included participants in ITT population (all participants who were randomized to study treatment) who had a confirmed objective response achieved by Week 19.

Posted

Median

95% Confidence Interval

weeks

55 weeks

ID	Title	Description
OG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
OG001	Bevacizumab-EU	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.

Secondary

Progression Free Survival Rate at 55 Weeks

This outcome measure refers to the possibility of being progression free at 55 weeks since start of study treatment, estimated from the Kaplan-Meier curve using the product-limit method.

The ITT population was used for analysis, and it included all participants who were randomized to study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

55 weeks

ID	Title	Description
OG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
OG001	Bevacizumab-EU	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.

Secondary

Survival Rate at 55 Weeks

This outcome measure refers to the possibility of being alive at 55 weeks since start of study treatment, estimated from the Kaplan-Meier curve using the product-limit method.

The ITT population was used for analysis, and it included all participants who were randomized to study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

55 weeks

ID	Title	Description
OG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
OG001	Bevacizumab-EU	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.

Secondary

Serum Concentration of Bevacizumab up to 1 Year

The analysis population included all participants in the per-protocol population (all participants who were randomized and received study treatment as planned and had no major protocol deviations) who had at least 1 drug concentration measurement after administration of study treatment.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose from Cycle 1 to Cycle 17, 2.5 hours post-dose in Cycle 1, and 1.5 hours post-dose in Cycle 5

ID	Title	Description
OG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
OG001	Bevacizumab-EU	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.

Secondary

Number of Participants With Anti-Drug Antibody (ADA)

ADA assay was performed using a sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) method, which used biotinylated- and ruthenium-labeled PF-06439535 as reagents. Samples with ADA titer greater than or equal to (>=) 2.29 were considered positive.

The analysis population included all participants who were randomized and received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

55 weeks

ID	Title	Description
OG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
OG001	Bevacizumab-EU	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.

Secondary

Number of Participants With Neutralizing Antibody (NAb)

Only samples that were confirmed positive for ADA were further tested for NAb. The NAb analysis was conducted using a single validated quasi-quantitative enzyme-linked immunosorbent assay (ELISA) that utilized PF-06439535 as a reagent. Samples with NAb titer >=1.70 were considered positive.

The analysis population included all participants who had positive ADA results at any time point.

Posted

Count of Participants

Participants

55 weeks

ID	Title	Description
OG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
OG001	Bevacizumab-EU	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG0004 events2 affected356 at risk EG0016 events5 affected358 at risk EG00210 events7 affected714 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG0007 events5 affected356 at risk EG0017 events7 affected358 at risk EG00214 events12 affected714 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG0003 events2 affected356 at risk EG0010 events0 affected358 at risk EG0023 events2 affected714 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG0005 events4 affected356 at risk EG0018 events6 affected358 at risk EG00213 events10 affected714 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events1 affected356 at risk EG0011 events1 affected358 at risk EG0023 events2 affected714 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG0005 events3 affected356 at risk EG0013 events3 affected358 at risk EG0028 events6 affected714 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0011 events1 affected358 at risk EG0022 events2 affected714 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0011 events1 affected358 at risk EG0022 events2 affected714 at risk
Angina unstable	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Cardiac arrest	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0011 events1 affected358 at risk EG0022 events2 affected714 at risk
Cardiac failure	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0012 events2 affected358 at risk EG0022 events2 affected714 at risk
Cardiovascular insufficiency	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0011 events1 affected358 at risk EG0022 events2 affected714 at risk
Myocardial infarction	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0011 events1 affected358 at risk EG0022 events2 affected714 at risk
Right ventricular failure	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Colitis	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0012 events2 affected358 at risk EG0022 events2 affected714 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0003 events2 affected356 at risk EG0013 events2 affected358 at risk EG0026 events4 affected714 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Faecaloma	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Gastritis	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Ileus	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0012 events2 affected358 at risk EG0022 events2 affected714 at risk
Neutropenic colitis	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Peptic ulcer	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Small intestinal perforation	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Subileus	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0011 events1 affected358 at risk EG0022 events2 affected714 at risk
Asthenia	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0005 events4 affected356 at risk EG0011 events1 affected358 at risk EG0026 events5 affected714 at risk
Chest pain	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0011 events1 affected358 at risk EG0022 events2 affected714 at risk
Death	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events2 affected356 at risk EG0013 events3 affected358 at risk EG0025 events5 affected714 at risk
Disease progression	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0004 events4 affected356 at risk EG0015 events5 affected358 at risk EG0029 events9 affected714 at risk
General physical health deterioration	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Pain	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events2 affected356 at risk EG0011 events1 affected358 at risk EG0023 events3 affected714 at risk
Cholangitis acute	Hepatobiliary disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events2 affected356 at risk EG0010 events0 affected358 at risk EG0022 events2 affected714 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Anal infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Appendicitis perforated	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Bacteraemia	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Disseminated tuberculosis	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Febrile infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Gastroenteritis	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0004 events4 affected356 at risk EG0010 events0 affected358 at risk EG0024 events4 affected714 at risk
Infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Infectious pleural effusion	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0012 events2 affected358 at risk EG0023 events3 affected714 at risk
Lung abscess	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Lung infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0011 events1 affected358 at risk EG0022 events2 affected714 at risk
Oral fungal infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Pleural infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Pneumonia	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG00011 events8 affected356 at risk EG0016 events6 affected358 at risk EG00217 events14 affected714 at risk
Respiratory tract infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0002 events2 affected356 at risk EG0010 events0 affected358 at risk EG0022 events2 affected714 at risk
Sepsis	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0012 events2 affected358 at risk EG0022 events2 affected714 at risk
Septic shock	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Sinusitis	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Soft tissue infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0013 events2 affected358 at risk EG0024 events3 affected714 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Subarachnoid haemorrhage	Injury, poisoning and procedural complications	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0012 events1 affected358 at risk EG0022 events1 affected714 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Blood bilirubin increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Neutrophil count decreased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0011 events1 affected358 at risk EG0022 events2 affected714 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0005 events4 affected356 at risk EG0010 events0 affected358 at risk EG0025 events4 affected714 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0012 events2 affected358 at risk EG0022 events2 affected714 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Bone cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Non-systematic Assessment	EG0003 events2 affected356 at risk EG0012 events2 affected358 at risk EG0025 events4 affected714 at risk
Tumour necrosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Dizziness	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Headache	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0014 events3 affected358 at risk EG0024 events3 affected714 at risk
Mononeuropathy	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Paraesthesia	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Proteinuria	Renal and urinary disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Renal cyst	Renal and urinary disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Urinary retention	Renal and urinary disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events2 affected356 at risk EG0012 events2 affected358 at risk EG0024 events4 affected714 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events2 affected356 at risk EG0012 events1 affected358 at risk EG0024 events3 affected714 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events2 affected356 at risk EG0013 events2 affected358 at risk EG0025 events4 affected714 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events2 affected356 at risk EG0011 events1 affected358 at risk EG0023 events3 affected714 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0007 events7 affected356 at risk EG0012 events2 affected358 at risk EG0029 events9 affected714 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0003 events3 affected356 at risk EG0013 events3 affected358 at risk EG0026 events6 affected714 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events1 affected356 at risk EG0010 events0 affected358 at risk EG0022 events1 affected714 at risk
Brachiocephalic vein thrombosis	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Embolism arterial	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0011 events1 affected358 at risk EG0022 events2 affected714 at risk
Haemorrhage	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Hypertensive crisis	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Ischaemia	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk
Shock haemorrhagic	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected356 at risk EG0011 events1 affected358 at risk EG0021 events1 affected714 at risk
Subgaleal haematoma	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected356 at risk EG0010 events0 affected358 at risk EG0021 events1 affected714 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukopenia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG00044 events26 affected356 at risk EG00156 events30 affected358 at risk EG002100 events56 affected714 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG000130 events59 affected356 at risk EG001144 events66 affected358 at risk EG002274 events125 affected714 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG000122 events55 affected356 at risk EG001125 events66 affected358 at risk EG002247 events121 affected714 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG00045 events39 affected356 at risk EG00136 events27 affected358 at risk EG00281 events66 affected714 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG00059 events46 affected356 at risk EG00166 events48 affected358 at risk EG002125 events94 affected714 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG000111 events71 affected356 at risk EG001112 events69 affected358 at risk EG002223 events140 affected714 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG00052 events41 affected356 at risk EG00142 events33 affected358 at risk EG00294 events74 affected714 at risk
Asthenia	General disorders	MedDRA 20.1	Non-systematic Assessment	EG00078 events46 affected356 at risk EG00165 events43 affected358 at risk EG002143 events89 affected714 at risk
Fatigue	General disorders	MedDRA 20.1	Non-systematic Assessment	EG000110 events73 affected356 at risk EG00187 events71 affected358 at risk EG002197 events144 affected714 at risk
Pyrexia	General disorders	MedDRA 20.1	Non-systematic Assessment	EG00031 events24 affected356 at risk EG00141 events23 affected358 at risk EG00272 events47 affected714 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 20.1	Non-systematic Assessment	EG00026 events19 affected356 at risk EG00126 events22 affected358 at risk EG00252 events41 affected714 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG00095 events49 affected356 at risk EG00153 events39 affected358 at risk EG002148 events88 affected714 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG00094 events44 affected356 at risk EG00159 events37 affected358 at risk EG002153 events81 affected714 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG00046 events29 affected356 at risk EG00148 events32 affected358 at risk EG00294 events61 affected714 at risk
Blood creatinine increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG00028 events16 affected356 at risk EG00133 events21 affected358 at risk EG00261 events37 affected714 at risk
Platelet count decreased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG00031 events23 affected356 at risk EG00138 events19 affected358 at risk EG00269 events42 affected714 at risk
Weight decreased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG00043 events36 affected356 at risk EG00140 events29 affected358 at risk EG00283 events65 affected714 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG00076 events48 affected356 at risk EG00165 events46 affected358 at risk EG002141 events94 affected714 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG00082 events40 affected356 at risk EG00171 events43 affected358 at risk EG002153 events83 affected714 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG00058 events25 affected356 at risk EG00147 events23 affected358 at risk EG002105 events48 affected714 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG000131 events54 affected356 at risk EG001109 events49 affected358 at risk EG002240 events103 affected714 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG00023 events16 affected356 at risk EG00129 events23 affected358 at risk EG00252 events39 affected714 at risk
Headache	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG00035 events30 affected356 at risk EG00145 events37 affected358 at risk EG00280 events67 affected714 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG00067 events53 affected356 at risk EG00186 events65 affected358 at risk EG002153 events118 affected714 at risk
Paraesthesia	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG00064 events40 affected356 at risk EG00136 events31 affected358 at risk EG002100 events71 affected714 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG00045 events34 affected356 at risk EG00170 events46 affected358 at risk EG002115 events80 affected714 at risk
Polyneuropathy	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG00034 events23 affected356 at risk EG00122 events19 affected358 at risk EG00256 events42 affected714 at risk
Proteinuria	Renal and urinary disorders	MedDRA 20.1	Non-systematic Assessment	EG00050 events28 affected356 at risk EG00176 events34 affected358 at risk EG002126 events62 affected714 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG00053 events41 affected356 at risk EG00158 events47 affected358 at risk EG002111 events88 affected714 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG00038 events32 affected356 at risk EG00141 events35 affected358 at risk EG00279 events67 affected714 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG00051 events40 affected356 at risk EG00148 events32 affected358 at risk EG00299 events72 affected714 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG000216 events166 affected356 at risk EG001232 events165 affected358 at risk EG002448 events331 affected714 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG00010 events9 affected356 at risk EG00129 events21 affected358 at risk EG00239 events30 affected714 at risk
Hypertension	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG00083 events60 affected356 at risk EG001110 events62 affected358 at risk EG002193 events122 affected714 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG000196 events102 affected356 at risk EG001200 events106 affected358 at risk EG002396 events208 affected714 at risk

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D056831	Coordination Complexes

ID	Title	Description
BG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
BG001	Bevacizumab-EU	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PF-06439535	Participants received up to a maximum of 6 cycles of PF-06439535 (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by PF-06439535 monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	144	356	81	356	328	356
EG001	Bevacizumab-EU	Participants received up to a maximum of 6 cycles of Bevacizumab-EU (initial dose was 15 mg/kg) plus paclitaxel (initial dose was 200 mg/m*2) and carboplatin (initial dose was AUC 6, based on participant's pre-existing renal function and desired platelet nadir), followed by Bevacizumab-EU monotherapy until disease progression, unacceptable toxicity, discretion of the investigator, regulatory request, death, withdrawal of consent occurred. All 3 drugs were given by intravenous (IV) infusion on Day 1 in each 21-day cycle and dose reduction was allowed for paclitaxel and carboplatin in response to toxicity. Paclitaxel was administered before carboplatin.	149	358	80	358	333	358
EG002	Total	This reporting group include all participants who received at least 1 dose of study treatment from PF-06439535 and Bevacizumab-EU groups.	293	714	161	714	661	714